The aim of this study was to evaluate the safety of Commiphora swynnertonii stem bark exudates by determining its acute and sub-acute toxicity in mice and rats. The acute toxicity of exudates was administered to mice by oral administration of a single dose of tested concentrations and observed for 14 days. The doses were 500, 1000 and 3000mg/Kg body weight. The sub-acute toxicity test of the exudate was conducted on rats through a daily oral administration of various doses for 28 days. The doses were 250, 500 and 1000mg/Kg body weight. The physiological, behavioral and body weight change as well as relative weight of internal organs were subsequently recorded. Hematological, biochemical and histopathological parameters for rats used in the sub-acute toxicity assay were also measured at day 28. Results showed that, administration of up to 3000 mg/Kg body weight the C. swynnertonii exudates in mice did not result into any observable toxicity or mortality within the period of 14 days. Furthermore, the sub-acute toxicity test revealed that the exudates did not induce mortality neither behavioral nor physiological changes after 28 days. It was further observed that, the rat’s body and relative internal organs weight as well as hematological, biochemical and histopathological parameters did not change as results of receive the doses for the whole period of the study. Therefore this study has revealed that C. swynnertonii stem bark exudates is safe for oral administration at low and moderate doses.